In that application, included herein in its entirety by reference, antigen-specific (hereinafter referred to as "specific") immunosuppression and immunotolerization in subjects in need of the selective suppression of immune responses to defined antigens is achieved through the pharmaceutical use of CD8, and derivatives thereof. This therapeutic strategy is predicated upon our discovery that the CD8 molecule inhibits immune and other cells that are being costimulated with certain secondary molecules (hereinafter referred to as "ligands"; vide infra). Although a variety of immunosuppressive capabilities have been previously ascribed to T lymphocytes with a CD8-positive phenotype, the role of the CD8 molecule itself as a critical molecular determinant of inhibitory activity exerted by these cells was unknown until said disclosure. Moreover, prior to said disclosure of CD8's inhibitory ligand function, the only known function for CD8 was its molecular accessory function, wherein it plays an obligatory role in T cell activation through the T cell receptor complex.
At the present time, specific immunotolerization therapies, primarily centered around the administration of specific antigen in association with additional substances, are relatively ineffective. Therapies for transplant, allergic and other subjects in need of immunosuppression most commonly employ generalized, nonspecific immunosuppressive agents. These therapeutic agents, which include X-irradiation, cytotoxic drugs, cyclosporin A, corticosteroids, and antilymphocytic serum, suffer from significant side effects involving multiple immune and nonimmune organs. Furthermore, in the case of clinical transplantation, no effective strategies for biochemically altering grafts in vitro to prolong their survival in a host have been described.
An object of the present invention is to provide an effective process for specific immunosuppression and immunotolerance induction, which process comprises the use of CD8 compositions.
Another object of the present invention is to provide a process, using CD8 compositions, for generalized, nonspecific immunosuppression, which process suffers from fewer side effects than currently available processes, and permits more specific targeting of organs of the immune system than current therapies.
Yet another object of the present invention is to provide a process for biochemically altering grafts prior to transplantation, in a way which enables them to evade immunological rejection mechanisms, and thereby promote their engraftment, which process comprises the use of CD8 compositions.
Still another object of the present invention is to provide a process for prevention of graft versus host disease following bone marrow transplantation, which process comprises the use of CD8 compositions.
Still another object of the present invention is to provide a process for selective modulation of nonimmune cells, which process comprises the use of CD8 compositions.
Other objectives, features and advantages of the invention will be found throughout the following description and claims.